Publications by authors named "Jonas Petersen"

12 Publications

  • Page 1 of 1

Promiscuous phospholipid biosynthesis enzymes in the plant pathogen Pseudomonas syringae.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Jul 22;1866(7):158926. Epub 2021 Mar 22.

Microbial Biology, Ruhr University Bochum, Bochum, Germany. Electronic address:

Bacterial membranes are primarily composed of phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and cardiolipin (CL). In the canonical PE biosynthesis pathway, phosphatidylserine (PS) is decarboxylated by the Psd enzyme. CL formation typically depends on CL synthases (Cls) using two PG molecules as substrates. Only few bacteria produce phosphatidylcholine (PC), the hallmark of eukaryotic membranes. Most of these bacteria use phospholipid N-methyltransferases to successively methylate PE to PC and/or a PC synthase (Pcs) to catalyze the condensation of choline and CDP-diacylglycerol (CDP-DAG) to PC. In this study, we show that membranes of Pseudomonas species able to interact with eukaryotes contain PE, PG, CL and PC. More specifically, we report on PC formation and a poorly characterized CL biosynthetic pathway in the plant pathogen P. syringae pv. tomato. It encodes a Pcs enzyme responsible for choline-dependent PC biosynthesis. CL formation is catalyzed by a promiscuous phospholipase D (PLD)-type enzyme (PSPTO_0095) that we characterized in vivo and in vitro. Like typical bacterial CL biosynthesis enzymes, it uses PE and PG for CL production. This enzyme is also able to convert PE and glycerol to PG, which is then combined with another PE molecule to synthesize CL. In addition, the enzyme is capable of converting ethanolamine or methylated derivatives into the corresponding phospholipids such as PE both in P. syringae and in E. coli. It can also hydrolyze CDP-DAG to yield phosphatidic acid (PA). Our study adds an example of a promiscuous Cls enzyme able to synthesize a suite of products according to the available substrates.
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http://dx.doi.org/10.1016/j.bbalip.2021.158926DOI Listing
July 2021

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.

Int J Mol Sci 2021 Jan 2;22(1). Epub 2021 Jan 2.

Institut für Pharmakologie und Klinische Pharmazie, Goethe-Universität Frankfurt am Main, 60438 Frankfurt am Main, Hessen, Germany.

The sodium-activated potassium channel Slack (K1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.
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http://dx.doi.org/10.3390/ijms22010405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795269PMC
January 2021

Neuropathic and cAMP-induced pain behavior is ameliorated in mice lacking CNGB1.

Neuropharmacology 2020 07 6;171:108087. Epub 2020 Apr 6.

Institute of Pharmacology and Clinical Pharmacy, Goethe University, 60438, Frankfurt am Main, Germany.

Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expression of the channel subunits CNGA2, CNGA3, CNGA4 and CNGB1 in dorsal root ganglia, and of CNGA2 in the spinal cord, is transiently altered after peripheral nerve injury in mice. Specifically, we show using in situ hybridization and quantitative real-time RT-PCR that CNG channels containing the CNGB1b subunit are localized to populations of sensory neurons and predominantly excitatory interneurons in the spinal dorsal horn. In CNGB1 knockout (CNGB1) mice, neuropathic pain behavior is considerably attenuated whereas inflammatory pain behavior is normal. Finally, we provide evidence to support CNGB1 as a downstream mediator of cAMP signaling in pain pathways. Altogether, our data suggest that CNGB1-positive CNG channels specifically contribute to neuropathic pain processing after peripheral nerve injury.
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http://dx.doi.org/10.1016/j.neuropharm.2020.108087DOI Listing
July 2020

Correction: Gold-carbonyl group interactions in the electrochemistry of anthraquinone thiols self-assembled on Au(111)-surfaces.

Chem Sci 2019 Jun 9;10(21):5641. Epub 2019 May 9.

Department of Chemistry , Technical University of Denmark , Kemitorvet, Building 207 , 2800 Kgs. Lyngby , Denmark . Email:

[This corrects the article DOI: 10.1039/C9SC00061E.].
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http://dx.doi.org/10.1039/c9sc90101aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568279PMC
June 2019

Designing Poly-agonists for Treatment of Metabolic Diseases: Challenges and Opportunities.

Drugs 2019 Jul;79(11):1187-1197

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

Obesity, type 2 diabetes, and the numerous associated metabolic co-morbidities are growing global threats to public health. Despite recent progress in pharmacotherapies for metabolic diseases, the current treatment options have limited efficacy and provide mostly symptomatic relief with little or no impact on disease reversal. Thus, improved therapies are urgently needed. As a result, the scientific community has increasingly invested in leveraging new pathophysiological insights into more efficacious pharmacotherapies for metabolic complications. A heightened understanding of the large, interindividual variation in responsiveness to certain metabolic medicines combined with advances in engineering multi-agonist candidates are important steps towards this goal. Additionally, the emerging pharmacological concept of peptide-mediated targeting of small molecules for tissue-specific delivery holds promise for more powerful treatment solutions in the future. In this review, we summarize recent advances in medicinal chemistry and molecular pharmacology that have enabled the engineering of several, novel, poly-agonist drug candidates for treatment of metabolic diseases, and we discuss the recent results from clinical trials assessing the efficacy and safety of glucagon-like peptide (GLP)-1/glucagon and GLP-1/GIP co-agonists.
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http://dx.doi.org/10.1007/s40265-019-01153-6DOI Listing
July 2019

Gold-carbonyl group interactions in the electrochemistry of anthraquinone thiols self-assembled on Au(111)-surfaces.

Chem Sci 2019 Apr 4;10(14):3927-3936. Epub 2019 Mar 4.

Department of Chemistry , Technical University of Denmark , Kemitorvet, Building 207 , 2800 Kgs. Lyngby , Denmark . Email:

New anthraquinone derivatives with either a single or two thiol groups (AQ1 and AQ2) were synthesized and immobilized in self-assembled monolayers (SAMs) on Au(111) electrodes Au-S bonds. The resultant AQ1- and AQ2-SAMs were studied by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), which enabled mapping of the gold-carbonyl group interactions and other dynamics in the Au-S bound molecular framework. Understanding of these interactions is important for research on thiol-coated gold nanoclusters, since (I) anthraquinone derivatives are a major compound family for providing desired redox functionality in multifarious assays or devices, and (II) the gold-carbonyl interactions can strongly affect anthraquinone electrochemistry. Based on equivalent circuit analysis, it was found that there is a significant rise in polarization resistance (related to SAM structural reorganization) at potentials that can be attributed to the quinone/semi-quinone interconversion. The equivalent circuit model was validated by calculation of pseudocapacitance for quinone-to-hydroquinone interconversion, in good agreement with the values derived from CV. The EIS and CV patterns obtained provide consistent evidence for two different ECEC ( proton-controlled ET steps, PCET) pathways in AQ1- and AQ2-SAMs. Notably, it was found that the formal reorganization (free) energies obtained for the elementary PCET steps are unexpectedly small for both SAMs studied. This anomaly suggests high layer rigidity and recumbent molecular orientation on gold surfaces, especially for the AQ2-SAMs. The results strongly indicate that gold-carbonyl group interactions can be controlled by favorable structural organization of anthraquinone-based molecules on gold surfaces.
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http://dx.doi.org/10.1039/c9sc00061eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457334PMC
April 2019

Distinct functions of soluble guanylyl cyclase isoforms NO-GC1 and NO-GC2 in inflammatory and neuropathic pain processing.

Pain 2019 Mar;160(3):607-618

Pharmakologisches Institut für Naturwissenschaftler, Goethe-Universität, Frankfurt am Main, Germany.

A large body of evidence indicates that nitric oxide (NO)/cGMP signaling essentially contributes to the processing of chronic pain. In general, NO-induced cGMP formation is catalyzed by 2 isoforms of guanylyl cyclase, NO-sensitive guanylyl cyclase 1 (NO-GC1) and 2 (NO-GC2). However, the specific functions of the 2 isoforms in pain processing remain elusive. Here, we investigated the distribution of NO-GC1 and NO-GC2 in the spinal cord and dorsal root ganglia, and we characterized the behavior of mice lacking either isoform in animal models of pain. Using immunohistochemistry and in situ hybridization, we demonstrate that both isoforms are localized to interneurons in the spinal dorsal horn with NO-GC1 being enriched in inhibitory interneurons. In dorsal root ganglia, the distribution of NO-GC1 and NO-GC2 is restricted to non-neuronal cells with NO-GC2 being the major isoform in satellite glial cells. Mice lacking NO-GC1 demonstrated reduced hypersensitivity in models of neuropathic pain, whereas their behavior in models of inflammatory pain was normal. By contrast, mice lacking NO-GC2 exhibited increased hypersensitivity in models of inflammatory pain, but their neuropathic pain behavior was unaltered. Cre-mediated deletion of NO-GC1 or NO-GC2 in spinal dorsal horn neurons recapitulated the behavioral phenotypes observed in the global knockout. Together, these results indicate that cGMP produced by NO-GC1 or NO-GC2 in spinal dorsal horn neurons exert distinct, and partly opposing, functions in chronic pain processing.
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http://dx.doi.org/10.1097/j.pain.0000000000001440DOI Listing
March 2019

Oxidative Modification of Tryptophan-Containing Peptides.

ACS Comb Sci 2018 06 11;20(6):344-349. Epub 2018 May 11.

Department of Chemistry , Technical University of Denmark , DK-2800 Kongens Lyngby , Denmark.

We herein present a broadly useful method for the chemoselective modification of a wide range of tryptophan-containing peptides. Exposing a tryptophan-containing peptide to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) resulted in a selective cyclodehydration between the peptide backbone and the indole side chain of tryptophan to form a fully conjugated indolyl-oxazole moiety. The modified peptides show a characteristic and significant emission maximum at 425 nm, thus making the method a useful strategy for fluorescence labeling.
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http://dx.doi.org/10.1021/acscombsci.8b00014DOI Listing
June 2018

The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord.

Front Mol Neurosci 2018 8;11:19. Epub 2018 Feb 8.

Developmental Neurobiology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI ( and ) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice. Cholera toxin labeling in digits of the hind paw demonstrated an altered shape of sensory neuron termination fields in the spinal cord of conditional Npr2 mouse mutants. Behavioral testing of both sexes indicated that noxious heat sensation and nociception induced by chemical irritants are impaired in the mutants, whereas responses to cold sensation, mechanical stimulation, and motor coordination are not affected. Recordings from C-fiber nociceptors in the hind limb skin showed that Npr2 function was not required to maintain normal heat sensitivity of peripheral nociceptors. Thus, the altered behavioral responses to noxious heat found in mice is not due to an impaired C-fiber function. Overall, these data point to a critical role of axonal bifurcation for the processing of pain induced by heat or chemical stimuli.
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http://dx.doi.org/10.3389/fnmol.2018.00019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809486PMC
February 2018

K3.1 channels modulate the processing of noxious chemical stimuli in mice.

Neuropharmacology 2017 Oct 18;125:386-395. Epub 2017 Aug 18.

Pharmakologisches Institut für Naturwissenschaftler, Goethe-Universität, Fachbereich Biochemie, Chemie und Pharmazie, 60438 Frankfurt am Main, Germany; Institut für Pharmakologie und Toxikologie, Universität Witten/Herdecke, ZBAF, 58453 Witten, Germany.

Intermediate conductance calcium-activated potassium channels (K3.1) have been recently implicated in pain processing. However, the functional role and localization of K3.1 in the nociceptive system are largely unknown. We here characterized the behavior of mice lacking K3.1 (K3.1) in various pain models and analyzed the expression pattern of K3.1 in dorsal root ganglia (DRG) and the spinal cord. K3.1 mice demonstrated normal behavioral responses in models of acute nociceptive, persistent inflammatory, and persistent neuropathic pain. However, their behavioral responses to noxious chemical stimuli such as formalin and capsaicin were increased. Accordingly, formalin-induced nociceptive behavior was increased in wild-type mice after administration of the K3.1 inhibitor TRAM-34. In situ hybridization experiments detected K3.1 in most DRG satellite glial cells, in a minority of DRG neurons, and in ependymal cells lining the central canal of the spinal cord. Together, our data point to a specific inhibitory role of K3.1 for the processing of noxious chemical stimuli.
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http://dx.doi.org/10.1016/j.neuropharm.2017.08.021DOI Listing
October 2017

Rab7-a novel redox target that modulates inflammatory pain processing.

Pain 2017 07;158(7):1354-1365

Institute of Pharmacology, College of Pharmacy, Goethe University, Frankfurt am Main, Germany.

Chronic pain is accompanied by production of reactive oxygen species (ROS) in various cells that are important for nociceptive processing. Recent data indicate that ROS can trigger specific redox-dependent signaling processes, but the molecular targets of ROS signaling in the nociceptive system remain largely elusive. Here, we performed a proteome screen for pain-dependent redox regulation using an OxICAT approach, thereby identifying the small GTPase Rab7 as a redox-modified target during inflammatory pain in mice. Prevention of Rab7 oxidation by replacement of the redox-sensing thiols modulates its GTPase activity. Immunofluorescence studies revealed Rab7 expression to be enriched in central terminals of sensory neurons. Knockout mice lacking Rab7 in sensory neurons showed normal responses to noxious thermal and mechanical stimuli; however, their pain behavior during inflammatory pain and in response to ROS donors was reduced. The data suggest that redox-dependent changes in Rab7 activity modulate inflammatory pain sensitivity.
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http://dx.doi.org/10.1097/j.pain.0000000000000920DOI Listing
July 2017

Entanglement generated by dissipation and steady state entanglement of two macroscopic objects.

Phys Rev Lett 2011 Aug 17;107(8):080503. Epub 2011 Aug 17.

Niels Bohr Institute, Danish Quantum Optics Center QUANTOP, Copenhagen University, Copenhagen, Denmark.

Entanglement is a striking feature of quantum mechanics and an essential ingredient in most applications in quantum information. Typically, coupling of a system to an environment inhibits entanglement, particularly in macroscopic systems. Here we report on an experiment where dissipation continuously generates entanglement between two macroscopic objects. This is achieved by engineering the dissipation using laser and magnetic fields, and leads to robust event-ready entanglement maintained for 0.04 s at room temperature. Our system consists of two ensembles containing about 10(12) atoms and separated by 0.5 m coupled to the environment composed of the vacuum modes of the electromagnetic field. By combining the dissipative mechanism with a continuous measurement, steady state entanglement is continuously generated and observed for up to 1 h.
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http://dx.doi.org/10.1103/PhysRevLett.107.080503DOI Listing
August 2011
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